Several genes

Several genes are known to contain regions of trinucleotide
repeats. The number of repeats varies from person to person in
the general population, but within the normal range these
repeats are stably transmitted. When the number of repeats is
increased beyond the normal range, this region becomes
unstable with a tendency to increase in size when transmitted to
offspring. In some conditions there is a clear distinction
between normal and pathological alleles. In others, the
expanded alleles may act either as premutations or as full
pathological mutations. Premutations do not cause disease but
are unstable and likely to expand further when transmitted to
offspring. Once the repeat reaches a certain size it becomes a
full mutation and disease will occur. Since the age at onset and
severity of the disease correlate with the size of the expansion,
this phenomenon accounts for the clinical anticipation that is
seen in this group of conditions, where age at onset decreases
in successive generations of a family. There is a sex bias in the
transmission of the most severe forms of some of these
disorders, with maternal transmission of congenital myotonic
dystrophy and fragile X syndrome, but paternal transmission of
juvenile Huntington disease.